The purpose of this study is to determine the pathogenesis of gallstone formation and hepatic dysfunction in patients with sickle cell disease. Initially, clinical studies will be carried out to assess the true prevalence of cholelithiasis and liver disease in this condition. These rates, which will be compared with those found in patients with sicke cell trait and age-- and sex-matched controls, will be determined by obtaining a gallbladder series and a complete set of liver function tests in each participant. Factors affecting gallstone formation will then be compared in patients with sickle cell anemia or sickle trait and in controls by delineating them for each group, sub-divided into sub- groups based on the presence or absence of gallstones. First, the bilirubin and lipid composition of gallstones, and of gallbladder and hepatic bile will be determined by measurement of the concentrations of bilirubin, bile acids, cholesterol, and phospholipids in bile obtained at surgery for cholelithiasis or by duodenal drainage from patients without stones. Second, the role of biliary tract infection will be assessed by aerobic and anerobic cultures of surgically obtained bile. Third, the effect of diet and the magnitude of bilirubin and bile salt kinetics, using C14-cholic and H3-chenodeoxycholic acids and C-14- bilirubin, will be determined in patients who have surgically placed balloon-occludible, reinfusion T tubes and in volunteers utilizing the multi-lumen intestinal perfusion technique. Fourth, the effect of sickle cell crisis upon these parameters will be assessed by measring the carbon monoxide production rate and the bilirubin and lipid composition of bile-rich duodenal fluid in the same patients during and between crises. Fifth, the effect of age and sex will be evaluated by comparison of bile-rich duodenal fluid obtained by serial followup or pediatric and adult sickle cell patients. Using serial clinical, biochemical and histological followup, the natural history of hepatic dysfunction in sickle cell disease will be defined and varieties of dysfunction will be separated, facilitating easier diagnosis and suggesting treatment modalities. This comprehensive approach will define the incidence and role of disordered hepatobiliary function in sicke cell disease.